Restriction of essential amino acids dictates the systemic metabolic response to dietary protein dilution

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

Dokumenter

  • Yann W Yap
  • Patricia M Rusu
  • Andrea Y Chan
  • Barbara C Fam
  • Andreas Jungmann
  • Samantha M Solon-Biet
  • Christopher K Barlow
  • Darren J Creek
  • Cheng Huang
  • Ralf B Schittenhelm
  • Bruce Morgan
  • Dieter Schmoll
  • Kiens, Bente
  • Matthew D W Piper
  • Mathias Heikenwälder
  • Stephen J Simpson
  • Stefan Bröer
  • Sofianos Andrikopoulos
  • Oliver J Müller
  • Adam J Rose

Dietary protein dilution (DPD) promotes metabolic-remodelling and -health but the precise nutritional components driving this response remain elusive. Here, by mimicking amino acid (AA) supply from a casein-based diet, we demonstrate that restriction of dietary essential AA (EAA), but not non-EAA, drives the systemic metabolic response to total AA deprivation; independent from dietary carbohydrate supply. Furthermore, systemic deprivation of threonine and tryptophan, independent of total AA supply, are both adequate and necessary to confer the systemic metabolic response to both diet, and genetic AA-transport loss, driven AA restriction. Dietary threonine restriction (DTR) retards the development of obesity-associated metabolic dysfunction. Liver-derived fibroblast growth factor 21 is required for the metabolic remodelling with DTR. Strikingly, hepatocyte-selective establishment of threonine biosynthetic capacity reverses the systemic metabolic response to DTR. Taken together, our studies of mice demonstrate that the restriction of EAA are sufficient and necessary to confer the systemic metabolic effects of DPD.

OriginalsprogEngelsk
Artikelnummer2894
TidsskriftNature Communications
Vol/bind11
Udgave nummer1
Antal sider13
ISSN2041-1723
DOI
StatusUdgivet - 2020

Bibliografisk note

CURIS 2020 NEXS 191

ID: 243016879